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An Overview of Clinical and Pathological Characteristics and Survival Rate of Colorectal Cancer in Iran


1 Cancer Research Center, Omid Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IR Iran
2 Student Research Committee, Resident of Radiation Oncology, Shiraz University of Medical Sciences, Shiraz, IR Iran
3 Department of Radiation Oncology, Isfahan University of Medical Sciences, Isfahan, IR Iran
4 Colorectal Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran
*Corresponding author: Mohammad Mohammadianpanah, Colorectal Research Center, Shiraz University of Medical Sciences, P. O. Box: 71936, Shiraz, IR Iran. Tel: +98-7116125168, Fax: +98-7116474320, E-mail: mohpanah@gmail.com, mohpanah@sums.ac.ir.
Annals of Colorectal Research. 2(1): e17264 , DOI: 10.17795/acr-17264
Article Type: Review Article; Received: Dec 29, 2013; Revised: Feb 20, 2014; Accepted: Apr 12, 2014; epub: Mar 30, 2014;

Abstract


Context: Colorectal cancer is one of the most common cancers and the leading cause of cancer death in Iran. This study aimed to identify the clinical and pathological characteristics, as well as survival rate of colorectal cancer in Iran.

Evidence Acquisition: The articles published in PubMed without language and time restrictions were included in this review. Only original clinical articles were included in the review and non-clinical studies, including cellular, molecular, genetics, and animal reports, were excluded. The case reports, letters, reviews, and clinical reports with less than 100 patients were excluded, as well. All the clinical data regarding the patients’ demographics, tumor characteristics, and survival rate were collected.

Results: A total of 178 studies were identified at the initial step of literature search. After applying the inclusion and exclusion criteria, 27 studies, including 38073 patients were eligible. The mean age of the patients was 57.2 years, and the male-female ratio was 1.38. Colon, rectum, and rectosigmoid junction accounted for 58%, 28%, and 14% of all colorectal primary sites, respectively. Moreover, the average proportion of the patients with stages 0-I, II, III, and IV was 9%, 39%, 36%, and 16%, respectively. Besides, tumor grades 1, 2, and 3 were reported in 52%, 37%, and 11% of the patients, respectively. Adenocarcinoma (96.8%) was the most frequent histological type. The mean and median survival rate was 80.1 and 55.2 months, respectively. Additionally, the average 5-year overall survival rate was 52.5%.

Conclusions: In Iran, colorectal cancer tends to manifest at locally advanced stage with poor prognosis. Therefore, public health strategies, such as screening programs, should be planned for early detection of this aggressive neoplasm.

Keywords: Colorectal Neoplasms; Clinical Characteristics; Pathology; Survival

1. Context


Malignant neoplasms arising from colon, rectum, and anal canal are categorized as colorectal cancer; however, colorectal cancer is usually used for histological type of adenocarcinoma (1, 2). Colorectal cancer is the third most common cancer in men and the second one in women worldwide. This malignancy is the fifth most frequently diagnosed cancer and the leading cause of cancer death in developing countries (3). Based on the Iranian annual national cancer registration report, this neoplasm is the fifth common cancer in Iranian men and the third one in women (4).

There is a wide range of different regional incidence rates among continents and countries. The highest incidence rates have been found in Eastern European countries, Japan, New Zealand, Australia, Germany, and North America (America Africans). On the other hand, the lowest rates have been reported from Central and South America, Africa, as well as South and Central Asia (5). Although the incidence rate of colorectal cancer has been stabilized and declined in traditionally high-risk areas, such as North America and New Zealand, a rapid increase has been observed in low-risk Asian countries, such as Japan, Korea, and China. Changing toward western dietary and lifestyle, smoking, and obesity are believed to contribute to this increase in the incidence rates in these countries (5, 6).

Colorectal cancer tends to have a high mortality rate, and its outcome is closely related to the extent of lymph node involvement and disease stage at presentation (7). Abdominal pain, change in bowel habits, rectal bleeding, weakness, anemia, and weight loss are the most frequent symptoms in the patients with colorectal cancer. Moreover, alarm symptoms, such as dark red rectal bleeding and abdominal mass, are more specific than individual symptoms for diagnosing colorectal cancer. Symptomatic presentation is usually a manifestation of locally advanced disease (8).

Surgical resection is the mainstay of therapy in locoregional and eligible metastatic colorectal cancer (9). Colectomy, low anterior excision, or abdominoperineal resection may be performed through laparoscopic or open surgery for the patients with colorectal cancer (10, 11).

Some reports have suggested a higher colorectal mortality in men than women (12). In addition, age, tumor grade and differentiation, mucinous subtype, geographic region, total lymph node harvested, and lymph node ratio were found as prognostic factors for overall survival in the patients with colorectal cancer (7, 10, 13). There are some concerns regarding the adequacy of lymph node staging as well as different patterns of clinical and pathological features and outcomes of Iranian patients with colorectal cancer compared to other parts of the world (13-17).

We aim to conduct a survey of colorectal cancer reports of Iran for detailing the clinical as well as pathological features and outcomes of these patients.

2. Evidence Acquisition


The articles published in PubMed, including Iranian population studies, without language and time restrictions were included in this survey. Only original clinical articles were included and non-clinical studies, including cellular, molecular, genetics, and animal studies, were excluded. Case reports, letters, reviews, clinical reports with less than 100 patients, and statistical and epidemiologic studies lacking clinical data were excluded.

All the clinical data regarding the patients’ demographics, tumor characteristics, and survival rates were collected. In this review, all included studies were retrospective series, with relative similar follow-up and quality. Therefore, we performed summation of study results with simple weighting based on the sample sizes. The data were extracted from the eligible studies which included authors’ names, year of publication, study period, geographical region, authors’ institution, the number of patients, baseline characteristics, primary tumor site, preoperative stage of disease, histological type, tumor grade, and disease free and overall survival rates.

The following keywords were used in the article title or author’s affiliation: “colorectal cancer” or “colorectal carcinoma,” “colon cancer" or “colon carcinoma,” “rectal cancer” or “rectal carcinoma,” and “anal canal cancer” or “anal canal carcinoma,”, and “Iran”.

Then, two authors independently reviewed all the eligible studies and extracted the studies’ characteristics. Duplicated articles were checked regarding the authors, study population, publication year, and the study period and those with similar study populations but different authors, institutions, or study periods were included.

3. Results


3.1. Literature Search and Study Selection

Our initial PubMed search found 178 studies reporting on Iranian colorectal cancer. Among these, the majority of the references (n=92) identified with non-clinical abstracts that were excluded. Genetic, molecular, and cell studies were found to be the most frequent researches investigating colorectal cancer in Iran. Additional excluded references were ineligible clinical studies (n=59). The reports with inadequate sample sizes (< 100 cases), reviews, colorectal polyps, screening, and diagnostic methods were the most frequent excluded articles in this category.

Ultimately, 27 articles were found eligible (11, 13, 15, 16, 18-40) (Figure 1). All those articles were published from 2004 to 2013. Overall, the study periods were between 1986 and 2012; however, about two-third of all the articles had been accomplished after 2000. All the studies, but two, included both colon and rectal as the primary sites. Tehran (70%) and Research Center for Gastroenterology and Liver Disease (30%) were the most common geographic region and research center where the articles were reported from.

There was a significant population study overlap particularly among the reports from Tehran province. However, due to different authors, institutions, or study periods, these reports were included in the review (11, 13, 15, 16, 18-40) (Table 1).

Figure 1.
Flow Chart of the Literature Search Strategy
Table 1
. Twenty-Seven Large Clinical Studies on Colorectal Cancer in Iran Published in PubMed (11, 13, 15, 16, 18-40) a
3.2. Patients’ Demographic Characteristics

The mean age of the patients was 57.2 years (ranging from 47.3 to 63 years) in 26 studies with age information. Besides, the mean age of the male patients was slightly higher than that of the female patients (59.1 years vs. 57.6 years). A wide age range of 4 to 103 years was observed; nonetheless, the peak frequency was observed between the sixth and seventh decades of life in both sexes. The mean proportion of males was 56% across 26 eligible studies, and the average male-female ratio was 1.38 (range 098-1.66) (Table 2).

Table 2.
The Parents’ Demographic Characteristics in 26 Large Clinical Studies on Colorectal Cancer in Iran Published in PubMed (11, 13, 15, 16, 18-29, 31-40) a
3.3. Distribution of Primary Site

Out of the 27 eligible articles, distribution of the primary tumor site was partially or completely available in 17 studies, including 37716 patients. Colon, rectum, and rectosigmoid junction accounted for 58%, 28%, and 14% of all colorectal primary sites, respectively. By adding the rectosigmoid junction to rectal primary site, the mean proportion of the rectum as the primary site increased to 42%. Only 4 studies, including 7561 patients provided a detailed information regarding the sublocation of colon primary site as follows: Sigmoid colon 43%, ascending colon 21%, cecum 21%, descending colon 12%, and transverse colon 3% (11, 13, 15, 16, 18-29, 31-40).

3.4. Distribution of Disease Stage

In this review, 10 out of the 27 eligible studies had information on the disease stage. However, detailed information was available only for 3728 patients (87%), and the 605 remaining patients (13%) had no staging data. Accordingly, by excluding the patients with unknown staging status, the mean proportion of the patients with stage 0-I was 9%. The mean values for stages II, III, and IV were 39%, 36%, and 16%, respectively. (11, 13, 15, 19, 20, 24, 29, 31, 32, 37).

3.5. Tumor Grade

Out of the 27 eligible articles, 12 studies, including 5733 patients had information on tumor grade. In these studies, 1229 patients had unknown tumor grade. Therefore, the distribution of tumor grade among the 4504 patients was as follows: grade 1, 52%; grade 2, 37%; and grade 3 11% (11, 13, 15, 19, 20, 22, 24, 26, 31, 32, 37, 39).

3.6. Distribution of Histological Types

Histological type was available in 6 eligible studies, including 3811 cases. Accordingly, adenocarcinoma was the most frequent histological type and accounted for 96.8% of all colorectal cancers followed by lymphoma (1.5%) and squamous cell carcinoma (0.4%). Carcinoid tumor, malignant melanoma, and sarcoma were the uncommon histological types in this region (13, 15, 20, 27, 34, 35).

3.7. Mean, median, and Overall Survival

A total of 11 out of the 27 studies included information on the mean, median, or overall survival rates. The mean overall survival period in 7 studies with 4780 patients was 80.1 months (range: 42.8-119.7). In addition, the median overall survival in 5 studies with 4746 patients was 55.2 months (range: 42-94.5). Besides, the average 1-, 2-, 3-, 4-, 5-, 10-, and 15-year overall survival rates were 85.9%, 74%, 64.9%, 55.3%, 52.5%, 47.9%, and 25.9%, respectively (11, 26, 29, 31-34, 36-39) (Table 3).

Table 3.
The Mean, Median, and Overall Survival Rates of the Iranian Patients With Colorectal Cancer in 11 Large Clinical Studies Published in PubMed (11, 26, 29, 31-34, 36-39) a

4. Conclusion


In this research, we reviewed 27 eligible studies comprising 38073 patients to yield a summation of clinical and pathological characteristics and survival rates of colorectal cancer in Iran. In this study, the mean age of the patients was 57.2 years that showed at least a decade younger in comparison to the same patients in western countries. In Iran, the peak frequency was observed between the sixth and seventh decades of life in both sexes. In western countries, however, the peak frequency was observed between the seventh and eighth decades of life (41).

This difference may be due to the younger Iranian population or genetic factors (22, 42). In addition, in Iran, no significant difference was found between the rectal and colon primary sites regarding the patients’ mean age (42). This is, on the contrary, to the western countries in which the age of the patients with rectal cancer was lower than that of colon cases (41). In a study using the Surveillance, Epidemiology, and End Results (SEER) database, the patients in all Asian-American subgroups who lived in the U.S.A. were younger at diagnosis compared to non-Hispanic white patients (median age: 68 vs. 72 years). In addition, the Asian-American subgroups had more advanced diseases and better disease free survival rates compared to non-Hispanic white patients (43).

In Iran, the male-female ratio in the patients with colorectal cancer showed slight male predominance, which is in contrast to the West in which there is no significant sex predilection. In West, colon cancer is slightly more common in female patients, while rectal cancer in slightly more common among males (41, 44). Previous reports indicated a higher portion of the rectal primary site in Iranian population compared to the West (20, 22, 34).

In this study, rectum and rectosigmoid junction accounted for 42% of all colorectal primary sites. This proportion was compatible with the data from European countries, but higher than the U.S.A. (37, 41, 45, 46). Figure 2 A-C illustrates the distribution of the primary tumor sites of colorectal cancer in Iran, Europe, and the U.S.A.(46).

Stage distribution of colorectal cancer in Iran is somewhat different from the West. In the U.S.A., 25%, 32%, 24%, and 19% of the patients with colorectal cancer showed stages I, II, III, and IV, respectively. Table 4 compares the distribution of disease stage in Iran, Europe, and the U.S.A. (10, 46). In the current study, we found a lower proportion for stages, I and IV, but a higher proportion of stage III. The use of screening program in developed countries might have played an important role in detecting a higher percentage of stage I, and a lower percentage of stage III compared to our country (12, 47). In addition, the lack of optimal metastatic work-up, such as chest Computed Tomography (CT) scan and Integrated Positron Emission Tomography (PET-CT) scan, in our patients may be an important contribution to the lower proportion of stage IV in our reports.

Most colorectal cancers are well or moderately differentiated tumors. In one study, among the 146574 patients with colorectal cancer, 81% of cancers were well or moderately differentiated, and 19% were poorly differentiated (41). In the present study, 89% of all the tumors were well or moderately differentiated, and 11% were poorly differentiated that is compatible with the West. Adenocarcinoma consists of the vast majority of colorectal cancer worldwide (46). However, other histological types, such as squamous cell carcinoma and lymphomas, are uncommon (2, 34, 48). The histological types in this study were compatible to the literature. Accordingly, adenocarcinoma was the most frequent histological type followed by lymphoma and squamous cell carcinoma.

Colorectal cancer is an aggressive tumor with poor prognosis and decimal outcome particularly in advanced disease stage. In developing countries, 5-year overall survival rates for this neoplasm ranged from 28% to 42%, compared to more than 60% in developed countries, such as the U.S.A., Japan, and Switzerland (5, 6, 49, 50). In this survey, the average 5-year survival of the Iranian patients with colorectal cancer was 52.5% which was between the values obtained in European countries (43%) and the U.S.A. (62%) (5, 46). However, there are some concerns regarding the under reporting of colorectal cancer mortality in Iran. In a study, Pourhoseingholi et al. used a Bayesian approach to estimate the mortality rates in the patients with colorectal cancer and found a 30-40% underreported mortality records in colorectal cancer death (17). Therefore, healthcare policy revision for early detection of colorectal cancer, accurate staging, mortality recording, and registry is warranted.

In Iran, colorectal cancer tends to manifest at locally advanced stage with poor outcome. Therefore, public health strategies, such as screening programs, should be planned for early detection of this aggressive neoplasm. In addition, a well-designed population-based cancer registry with acceptable coverage is needed to improve cancer reporting in our country.

Figure 2.
Distribution of the Primary Sites of Colorectal Cancer in Iran (A), Europe (B), and the U.S.A. (C)
Table 4.
Distribution of the Stage of Colorectal Cancer in Iran, Europe, and the U.S.A. (10)

Acknowledgments

The authors would like to thank Ms. A. Keivanshekouh at the Research Improvement Center of Shiraz University of Medical Sciences for editing the manuscript.

Footnotes

Implication for policy/practice/research/medical education: Colorectal cancer is one of the most common and leading causes of cancer death in Iran. In Iran, colorectal cancer tends to present at locally advanced stage with poor prognosis. Therefore, public health strategies, like screening programs, should be planned for early detection of this aggressive neoplasm.
Authors’ Contribution: Sareh Hoseini: Involved in study design, literature review, data collection, writing and revising the manuscript, and approval of the final version. Leila Moadshoar: Involved in study conception and design, literature review, writing the manuscript and approval of the final version. Simin Hemati: Involved in study conception and design, literature review, writing the manuscript and approval of the final version. Mohammad Mohammadianpanah: Involved in study conception and design, data collection, literature review, writing and revising the manuscript, and approval of the final version.
Financial Disclosure: None of the authors had any conflict of interest, financial or otherwise.n;
Funding/Support: This study was supported by Colorectal Research Center, Shiraz University of Medical Sciences.

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Table 1

. Twenty-Seven Large Clinical Studies on Colorectal Cancer in Iran Published in PubMed (11, 13, 15, 16, 18-40) a

AuthorsYear of publicationStudy periodNumber of patients Primary tumor site Geographical region (Province)Authors’ institution
Samareh Pahlavan (18)20051996-20001628colorectalMultiple provincesbMulticenter
Omranipour (19)20121994-2009442colorectalTehranCancer Institute of Tehran
Mahmodlou (20)20122001-2008546colorectalWest AzerbaijanWest Azerbaijan
Foroutan (21)20081989–2004977colorectalTehranSBMUH
Safaee (22)20082000-20071138colorectalTehranRCGELD
Nikbakht (23)20132001-2010792colorectalKermanResearch Center for Modeling
Ansari (16)20061996-20002055colorectalMultiple provincescMulticenter
Forootan (24)20122008-2012200colorectalTehranImam Hossein Hospital
Ghabeljoo (25)20112002-2007748colorectalTehranRCGELD
Aghili (15)20101999-2005130colorectalTehranIHSTHs
Safaee (26)20102002-2008110colorectalTehranRCGELD
Hosseini (27)20041980–2000328colorectalShirazColorectal Research Center
Safaee (28)20122005-200919617colorectalINCRcINCR
Aryaie (29)20132004-2008227colorectalGolestanGRCGEH
Fatemi (30)2010Not mentioned355colorectalTehranRCGELD
Asghari-Jafarabadi (31)20092002-20071219colorectalTehranRCGELD
Moghimi-Dehkordi (32)20082002-20071127colorectalTehranRCGELD
Mehrkhani (33)20081999-20021090colorectalTehranShariati Hospital
Moradi (34)20092000-20052192colorectalINCRdINCR
Samareh Pahlavan (35)20062000-2003200colorectalTehranShohada General Hospital
Gohari (36)20112002-20071007colorectalTehranRCGELD
Omidvari (11)20132004-2010153RectumShirazColorectal Research Center
Jafari Nadoshan (37)2013Not mentioned128RectumTehranCancer Institute of Tehran
Heidarnia (38)20132005-2006559colorectalTehranCRC of SBUMS
Fazeli (13)20071995-2001419colorectalTehranIKHCI
Haghighi (39)20082003-2008121colorectalTehranTaleghani hospital
Safaee (40)2010Not mentioned393colorectalTehranRCGELD
Overall2004-20131989-201239701colorectalIran-
a Abbreviations: CRC of SBUMS, cancer research center of Shahid Beheshti University of Medical Science; GRCGEH, Golestan Research Center of Gastroenterology and Hepatology; IHSTH, Imam Hussein and Shohadaye-Tajrish hospitals; IKHCI, Imam Khomeini Hospital and Cancer Institute; INCR, Iranian National Cancer registry; pts, patients; RCGELD, Research Center for Gastroenterology and Liver Disease; SBMUH, Shahid Beheshti Medical University hospitals.
b Including Mazandaran, Golestan, Ardabil, and Kerman.
c including Gilan, Mazandaran, Golestan.
d INCR, Ardabil, and Kerman.

Table 2.

The Parents’ Demographic Characteristics in 26 Large Clinical Studies on Colorectal Cancer in Iran Published in PubMed (11, 13, 15, 16, 18-29, 31-40) a

AuthorsNumber of patients Number of MenMale/Female ratioMean ageMale mean age Female mean ageMinimum ageMaximum age
Samareh Pahlavan (18)16289351.3557----
Omranipour (19)4422200.9953--1888
Mahmodlou (20)5463061.2855.2----
Foroutan (21)9775341.21-----
Safaee (22)11386961.5754.154.353.9--
Nikbakht (23)7924131.0959.4--1893
Ansari (16)205511291.2257----
Forootan (24)2001151.3557.1----
Ghabeljoo (25)748--53.9----
Aghili (15)130731.2849.7----
Safaee (26)110691.6850.1----
Hosseini (27)3281861.3154.956.752.31490
Safaee (28)19617109851.2758.959.658.1--
Aryaie (29) 2271381.5554--1485
Asghari-Jafarabadi (31) 12197201.4454----
Moghimi-Dehkordi (32)11276901.5853.6--1494
Mehrkhani (33)10907412.1250.5----
Moradi (34)219212351.2957.8--4103
Samareh Pahlavan (35)2001141.3355.155.754.31390
Gohari (36)10076281.6653.2----
Omidvari (11) 153891.3957--2384
Jafari Nadoshan (37)128671.0949--1685
Heidarnia (38)5592991.1563--2388
Fazeli (13)4192231.1352.353.751.21483
Haghighi (39)121600.9847.3--2278
Safaee (40)3932311.4253.5----
Total36798208961.38 b57.259.157.64103
a Abbreviations: pts, patients.
b For this mean value, Ghabeljoo’s study was excluded.

Table 3.

The Mean, Median, and Overall Survival Rates of the Iranian Patients With Colorectal Cancer in 11 Large Clinical Studies Published in PubMed (11, 26, 29, 31-34, 36-39) a

AuthorsNumber of patientsMean OS, moMedian OS, moOverall Survival Rates, %
1-y2-y3-y4-y5-y10-y15-y
Safaee (26)11091.548.692.6-----15
Aryaie (29)22743.442.871.8-80.1-41.3--
Asghari-Jafarabadi (31)1219119.7-93.1---42.6--
Moghimi-Dehkordi (32)1127105.194.591.186.278.57267.4--
Mehrkhani (33)109042.844.372-73.1-6147.925.9
Moradi (34)2192-4284.9-54-47--
Gohari Mahmood (36)100751.7-90.767.255.246.142.3--
Omidvari (11)153----71-46.7--
Jafari Nadoshan (37)128--89.8---69.4--
Heidarnia (38)559------26.5--
Haghighi (39)121------68.3--
Total 793380.155.285.97464.955.352.547.925.9
a Abbreviations: OS, Overall Survival.

Table 4.

Distribution of the Stage of Colorectal Cancer in Iran, Europe, and the U.S.A. (10)

AuthorsNumber of patients Stage
0-I, %II, %III, %IV, %Unstaged, %
Iran 3728733341313
Europe24921434212110
USA 11191243023185

Figure 1.

Flow Chart of the Literature Search Strategy
†, Screening and diagnostic methods and colorectal polyps were the most frequent in this category.

Figure 2.

Distribution of the Primary Sites of Colorectal Cancer in Iran (A), Europe (B), and the U.S.A. (C)